pten

PTEN is a tumor suppressor gene that encodes a lipid and protein phosphatase. It resides on chromosome 10q23.3 and is expressed in many tissues. The PTEN protein dephosphorylates PIP3 to PIP2, antagonizing PI3K/AKT/mTOR signaling. Through this activity it helps regulate cell growth, survival, and metabolism. In addition, PTEN contributes to genomic stability, DNA repair, cell migration, and cell cycle control.

PTEN is a 403-amino-acid protein containing an N-terminal phosphatase domain and a C2 domain that targets membrane association, with a regulatory C-terminal tail. The active-site motif is HCXXGXXR, characteristic of dual-specificity phosphatases. PTEN also has a PDZ-binding motif at the extreme C terminus, enabling interactions with scaffold proteins. Activity and localization are controlled by phosphorylation, oxidation, ubiquitination (notably by NEDD4-1), and proteasomal degradation. PTEN activity is modulated at transcriptional and post-translational levels, with p53 and other factors influencing expression.

Clinically, PTEN loss or mutation occurs in many cancers, contributing to hyperactive PI3K/AKT signaling. Germline PTEN mutations cause PTEN hamartoma tumor syndromes, including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome, with elevated lifetime cancer risk. Somatic alterations are common in glioblastoma, endometrial, prostate, and breast cancers. PTEN status is used as a biomarker of prognosis and may influence response to therapies targeting the PI3K/AKT/mTOR pathway; resistance often involves alternative signaling routes.

PTEN was identified in 1997 as a tumor suppressor gene deleted on chromosome 10 and named for its phosphatase activity and tensin homology.